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体重指数和体重对中国汉族不稳定型心绞痛患者替格瑞洛血浆浓度及血小板聚集率的影响

Effects of Body Mass Index and Body Weight on Plasma Concentration of Ticagrelor and Platelet Aggregation Rate in Patients with Unstable Angina in a Chinese Han Population.

作者信息

Guo Houling, Li Qingqi, He Fei, Cheng Cheng, Wang Min, Xu Banglong, Wang Xiaochen, Sheng Jianlong

机构信息

Department of Cardiology, The Second Affiliated Hospital of Anhui Medical University, 230601 Hefei, Anhui, China.

出版信息

Rev Cardiovasc Med. 2024 Mar 4;25(3):83. doi: 10.31083/j.rcm2503083. eCollection 2024 Mar.

Abstract

BACKGROUND

The aim of this study was to investigate the impact of body mass index (BMI) and body weight on the concentrations of ticagrelor and the ticagrelor metabolite, AR-C124910XX, as well as the platelet aggregation rate (PAR) in a Chinese Han population with unstable angina (UA). Specifically, it focused on these parameters following the administration of dual antiplatelet therapy (DAPT) comprising aspirin and ticagrelor.

METHODS

A total of 105 patients with UA were included in the study. Measurement of the platelet aggregation rate induced by adenosine diphosphate (PAR-ADP) was performed before, as well as 3 and 30 days after DAPT treatment. The plasma concentrations of ticagrelor and AR-C124910XX were detected at 3 and 30 days after DAPT treatment. We conducted correlation analyses to assess the effects of BMI and body weight on the concentrations of ticagrelor and AR-C124910XX, on PAR-ADP, and on the inhibition of platelet aggregation induced by adenosine diphosphate (IPA-ADP) at both 3 and 30 days after DAPT treatment.

RESULTS

The BMI and body weight were positively correlated with baseline PAR-ADP ( = 0.205, = 0.007; = 0.122, = 0.022). The PAR-ADP at 3 and 30 days after DAPT treatment were significantly lower than at baseline (61.56% 10.62%, 8.02% 7.52%, 12.90% 7.42%, 0.001). There was a negative correlation between body weight and the concentrations of ticagrelor and AR-C124910XX at 3 days following DAPT treatment ( = -0.276, 0.001; = -0.337, 0.001). Additionally, BMI showed a similar negative correlation with the concentrations of ticagrelor and AR-C124910XX ( = -0.173, = 0.009; = -0.207, = 0.002). At 30 days after treatment, both body weight and BMI were negatively correlated with ticagrelor ( = -0.256, 0.001; = -0.162, = 0.015) and its metabolite ( = -0.352, 0.001; = -0.202, = 0.002). Body weight was positively correlated with PAR-ADP ( = 0.171, = 0.010) and negatively correlated with IPA-ADP ( = -0.163, = 0.015) at 30 days after treatment. Similarly, BMI was positively correlated with PAR-ADP ( = 0.217, = 0.001) and negatively correlated with IPA-ADP ( = -0.211, = 0.001) at the same time point.

CONCLUSIONS

BMI and body weight are key factors influencing the pharmacokinetics and pharmacodynamics of ticagrelor in Chinese Han patients with UA following DAPT treatment that includes ticagrelor. Both BMI and body weight were positively correlated with PAR-ADP at baseline and 30 days after DAPT treatment.

CLINICAL TRIAL REGISTRATION

ChiCTR2100044938, https://www.chictr.org.cn/.

摘要

背景

本研究旨在探讨体重指数(BMI)和体重对替格瑞洛及其代谢产物AR-C124910XX浓度,以及对中国汉族不稳定型心绞痛(UA)患者血小板聚集率(PAR)的影响。具体而言,重点关注在给予包括阿司匹林和替格瑞洛的双联抗血小板治疗(DAPT)后这些参数的变化。

方法

本研究共纳入105例UA患者。在DAPT治疗前、治疗后3天和30天测量二磷酸腺苷诱导的血小板聚集率(PAR-ADP)。在DAPT治疗后3天和30天检测替格瑞洛和AR-C124910XX的血浆浓度。我们进行相关性分析,以评估BMI和体重对DAPT治疗后3天和30天替格瑞洛和AR-C124910XX浓度、PAR-ADP以及二磷酸腺苷诱导的血小板聚集抑制率(IPA-ADP)的影响。

结果

BMI和体重与基线PAR-ADP呈正相关(r = 0.205,P = 0.007;r = 0.122,P = 0.022)。DAPT治疗后3天和30天的PAR-ADP显著低于基线水平(61.56% ± 10.62%,8.02% ± 7.52%,12.90% ± 7.42%,P < 0.001)。DAPT治疗后3天,体重与替格瑞洛和AR-C124910XX浓度呈负相关(r = -0.276,P < 0.001;r = -0.337,P < 0.001)。此外,BMI与替格瑞洛和AR-C124910XX浓度也呈类似的负相关(r = -0.173,P = 0.009;r = -0.207,P = 0.002)。治疗后30天,体重和BMI均与替格瑞洛(r = -0.256,P < 0.001;r = -0.162,P = 0.015)及其代谢产物(r = -0.352,P < 0.001;r = -0.202,P = 0.002)呈负相关。治疗后30天,体重与PAR-ADP呈正相关(r = 0.171,P = 0.010),与IPA-ADP呈负相关(r = -0.163,P = 0.015)。同样,在同一时间点,BMI与PAR-ADP呈正相关(r = 0.217,P = 0.001),与IPA-ADP呈负相关(r = -0.211,P = 0.001)。

结论

BMI和体重是影响接受含替格瑞洛DAPT治疗的中国汉族UA患者替格瑞洛药代动力学和药效学的关键因素。BMI和体重在基线及DAPT治疗后30天均与PAR-ADP呈正相关。

临床试验注册

ChiCTR2100044938,https://www.chictr.org.cn/

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d853/11263822/37da8a4f74f2/2153-8174-25-3-083-g1.jpg

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